Combined data from LDL composition and size measurement are compatible with a discoid particle shape

Area of Science:

• Lipid biochemistry
• Structural biology
• Cardiovascular research

Background:

• Low-density lipoprotein (LDL) size is typically measured as diameter, assuming a spherical shape.
• Cryoelectron microscopy and crystallographic data suggest LDL may have a discoid (flattened disc) shape.
• Investigating LDL particle geometry is crucial for understanding its role in cardiovascular health.

Purpose of the Study:

• To investigate the geometry of LDL particles by integrating lipid composition data with size measurements.
• To determine if LDL particles are better represented as spherical or discoid.
• To identify key lipid components influencing LDL shape and dimensions.

Main Methods:

• Measured mean LDL diameter in 160 samples using high-performance gel-filtration chromatography (HPGC).
• Calculated particle volume based on LDL lipid composition.
• Modeled LDL shape as both spherical and discoid to compare calculated diameters and heights with HPGC measurements.

Main Results:

• Spherical shape assumption showed poor correlation (R² = 0.36) between calculated and measured diameters.
• Discoid shape model yielded diameter (20.9 nm) and height (12.1 nm) not significantly related to each other.
• LDL core lipids primarily determined particle height (R² = 0.83), while free cholesterol determined diameter (R² = 0.54).

Conclusions:

• Combined composition and size data support a discoid model for LDL particles.
• Propose a structural model where free cholesterol significantly impacts LDL shape and diameter.
• This finding refines our understanding of LDL structure and its implications for cardiovascular disease.